Fish Immunology and Pathology Laboratory, Animal Health Research Center (CISA-INIA), Madrid, Spain.
Front Immunol. 2019 Mar 26;10:584. doi: 10.3389/fimmu.2019.00584. eCollection 2019.
Oligodeoxynucleotides (ODN) containing unmethylated CpG motifs have been widely postulated as vaccine adjuvants both in mammals and teleost fish. However, to date, the effects that CpGs provoke on cells of the adaptive immune system remain mostly unexplored in fish. Given that rainbow trout () IgM B cells from spleen and blood transcribe high levels of toll like receptor 9 (TLR9), the receptor responsible for CpG detection in mammals, in the current work, we have investigated the effects of CpGs on both spleen and blood IgM B cells from this species. CpGs were shown to exert strong proliferative effects on both spleen and blood IgM B cells, also increasing their survival. The fact that CpGs increase the size of IgM B cells, reduce the expression of surface IgM and IgD and up-regulate the number of IgM-secreting cells strongly suggest that IgM B cells differentiate to plasmablasts/plasma cells in response to CpG stimulation. Additionally, CpGs were shown to modulate the antigen presenting capacities of trout IgM B cells through an increased surface MHC II expression and transcriptional up-regulation of co-stimulatory molecules, although in this case, significant differences were observed between the effects exerted on spleen and blood cells. Similarly, differences were observed between spleen and blood IgM B cells when CpG stimulation was combined with B cell receptor (BCR) cross-linking. Finally, CpGs were also shown to affect innate functions of teleost IgM B cells such as their phagocytic capacity. These results demonstrate that CpGs regulate many adaptive and innate functions of teleost B cells, supporting their inclusion as adjuvants in novel vaccine formulations.
含未甲基化 CpG 基序的寡脱氧核苷酸 (ODN) 已被广泛推测为哺乳动物和硬骨鱼的疫苗佐剂。然而，迄今为止，CpG 对鱼类适应性免疫系统细胞的影响在很大程度上仍未得到探索。鉴于虹鳟 () 脾脏和血液中的 IgM B 细胞转录高水平的 Toll 样受体 9 (TLR9)，这是哺乳动物中负责检测 CpG 的受体，在当前的工作中，我们研究了 CpG 对这种鱼类的脾脏和血液 IgM B 细胞的影响。CpG 对脾脏和血液 IgM B 细胞均表现出强烈的增殖作用，同时也提高了它们的存活率。CpG 增加 IgM B 细胞的大小、降低表面 IgM 和 IgD 的表达并上调 IgM 分泌细胞的数量这一事实强烈表明，IgM B 细胞在 CpG 刺激下分化为浆母细胞/浆细胞。此外，CpG 通过增加表面 MHC II 表达和共刺激分子的转录上调来调节硬骨鱼 IgM B 细胞的抗原呈递能力，尽管在这种情况下，在脾脏和血液细胞上观察到的效果存在显著差异。同样，当 CpG 刺激与 B 细胞受体 (BCR) 交联结合时，在脾脏和血液 IgM B 细胞之间也观察到差异。最后，CpG 还被证明会影响硬骨鱼 IgM B 细胞的先天功能，如吞噬能力。这些结果表明，CpG 调节硬骨鱼 B 细胞的许多适应性和先天功能，支持将其作为新型疫苗制剂的佐剂。
